Expansion of current reactivity umpolung of aldehydes catalyzed by chiral nucleophilic carbenes promises to reveal new reactivity and lead to novel bond disconnections relevant to the synthesis of a number of biologically significant targets. Reaction with a nucleophilic carbene transforms an electrophilic aldehyde into a nuclephile acyl anion equivalent which can be intercepted with a variety of electrophiles, providing a novel means of forming carbon-carbon bonds. If conducted using a chiral nucleophilic carbene as catalyst, we expect to induce asymmetry into the subsequent bond-forming event. These reactions will be applied to the synthesis of challenging, biologically active natural products. The specific goals of this research are as follows: 1) apply the asymmetric Stetter reaction to alkaloidal substrates to generate novel architectures and develop domino processes using these approaches; 2) develop the diastereoselective asymmetric Stetter reaction, which will be able to effect the formation of multiple contiguous stereocenters in a single operation; 3) use the asymmetric Stetter reaction in the synthesis of the angiogenesis inhibitor azaspirene; 4) design and execute a rapid approach to the stereochemically complex alkaloid asparagamine using the diastereoselective asymmetric Stetter reaction; 5) apply the asymmetric Stetter reaction to the synthesis of crinamine 1 and viridin using orthoquinones and dienones as electrophiles; 6) explore aldehyde umpolung redox chemistry by exploiting the large negative oxidation potential of the nucleophilic alkene and internal redox systems.